1 -Methoxy-10-methylacridone

Alkaloids considered in this section derive biogenetically from 1,3-dihydroxy-lO-methylacridone (19) and 1,3-dihydroxyacridone (22) by simple deoxygenation and/or oxidation of the acridone aromatic skeleton. Subsequent O-alkylation very often takes place, and most natural acridones bear methoxy or methylenedioxy substituents. A few, exemplified by vebilocine (27) (94), evoprenine (28) (95), and 3-graanyloxy-l-hydroxy-4-methoxy-10-methylacridone (29) (96), are also substituted by prenyloxy or geranyloxy groups. 

A further study of the root alkaloids of Ruta graveolens has resulted in the identification of a new chlorine-containing acridone (31), named iso-gravacridonchlorine.29 The same source yielded an inseparable mixture of alkaloids, shown by n.m.r. spectroscopy to consist of the new compound furacridone (32) and the known compound l-hydroxy-3-methoxy-N-methylacridone (29 R = H) in a ratio of 4 1. 

Pharmazie, 1975, 30, 753). Two new acridones, l-hydroxy-3,4-dimethoxy-lO-methylacridone (25) and l-hydroxy-3-geranyloxy-4-methoxy-lO-methylacridone (26) occur in extracts of the plant Sarcomelicope leiocarpa indigenous to New Caledonia together with eight other known structures (G. Baudouin et al., J.nat. Prod., 1985, 48, 260). 

Five acridone alkaloids were obtained previously from the bark of Teclea boiviniana cf. Vol. 6, p. 108) a recent investigation showed that the constituents of the leaves are similar, and resulted in the isolation of arborinine (37 R = H), tecleanthine (38 R = H, R = OMe), evoxanthine (38 R = R = H), 6-methoxytecleanthine (38 R = R = OMe), and 1,3,4-trimethoxy-iV-methyl-acridone (39 R = Me, R = OMe). The latter compound has not been obtained previously from a natural source. The n.m.r. and mass spectra indicated that the new alkaloid was a trimethoxy-iV-methylacridone and that ring A was unsubstituted. The three possible acridones had been synthesized earlier, and from melting-point data the alkaloid appeared to be the 1,3,4-trimethoxy-derivative this was confirmed by synthesis using a modification of the published procedures. 1,2,3-Trimethoxy-iV-methylacridone (37 R = Me), previously isolated from Evodia alata, has now been obtained from Melicope leratii. The known alkaloids melicopidine (40 R = Me, R = OMe) and xanthovedine (40 R = R = H) were also shown to be constituents of M. leratii. Arborinine (37 R = H) has been obtained from Vepris pilosa and from Ruta chalapensis. Other known acridone alkaloids isolated from a new source include the l-hydroxy-3-methoxy-deriva-tive (39 R = R = H) and its methyl ether (39 R = Me, R = H), from Vepris pilosa. ... 

Full accounts are not available of the synthesis of acridones by the cyclisation, with sodium hydride in dimethyl sulphoxide, of 2-methoxy-benzophenones containing 2 -acetamido- or 2 -methylamino-groups (c/. Vol. 7, p. 90) the alkaloids (41 R = Me) and l,3-dimethoxy-7V-methylacridone have been prepared by this route. ... 

Trihydroxy-4-methoxy-10-methyl-2,8-bw(3-methylbut-2-enyl) acridin-9( 10/7)-one, 1,5 -dihydroxy-2,3 -dimethoxy-10-methyl-9-acridone, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-l 1-methoxy-10-methylfuro[3,2-b]acridin-5(1077)-one, 3,4-Dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2/7-pyrano[2,3-a]acridin-12(7/7)-one, 3,4-Dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2/7-pyrano[2,3-a]acridin-12(7/7)-one, l-hydroxy-3-methoxy-10-methyl-9-acridone, 1 -hydroxy-2,3 -dimethoxy-10-methyl-9-acridone, 1 -hydroxy-A-methylacridone, l-methyl-2-[(Z)-pentadec-9-enyl]quinolin-4(l/7)-one,... 

Anti-HIV activity 1 -Hydroxy-W-methylacridone, 2-(pent-1 -enyl)quinoline, 2-(pent-2-en) quinolin, 2-acetyl-4(3H)-quinazolinone, 2- -pentylquinoline, 3-prenyl-4-prenyloxyquinolin-2-one, 4-methoxy-l-methylquinolin-2-one, )V-methyl-3,3-diprenylquinoline-2,4-dione, buchapine, y-fagarine, haplopine, (-1-)-platydesmine, uranidine [28, 30, 34, 38,40,41],... 

Deoxygenated products have a restricted distribution. Acridone itself (1) was isolated from Toddalia acukata (97) and Thamnosma montana (98), which also contains 10-methylacridone (30) (99, 100). Alkaloids lacking oxygenated substitution at C-3 include 1-hydroxyacridone, 1,7-dihydroxyacridone, and 1,8-dihydroxyacridone derivatives. It should be noted that 1-methoxy-10-methylacridone (31) and 1,8-dihydroxyacridone (32) were isolated from Samadera aff. bidwillii, the only species of the Simaroubaceae which has afforded this type of secondary metabolite (101). 

Dihydroxy-2-methoxy-l 0-methylacridone C15H13NO4 MW 271 spectral data. 144 source 144... 

This versatile methodology was successfiiUy q[>plied, with slight modifications, for the synthesis of a number of other aciidone alkaloids, including l-hydroxy-3-methoxy-lO-methylacridone (48) 301), 1,3-dimethoxy-lO-methylacridone (53) 301, 302), 1,3-dihydroxy-lO-methylacridone (19) 301, 302), 1,2,3-trimethoxy-lO-methylacridone (73) 303), xanthoxoline (58) 30S), and l,5-dihydn)xy-2,3-dimethoxy-lO-methylacridone (S-hydroxyaiborinine) (75) 188). 

Cyclization of a substituted 1 -aiylanthranilamide was the key step for the synthesis of citrusinine-I (76) described by Kato ei al. (312). The required 2-(2-hydroxyphenylamino)-3,4,6-trimethoxy-Af -dimethylbenzamide (235) was obtained by Ullmann reaction of 2-aminophenol with 2-iodo-3,4,6-trimethoxy-iV -dimethylbenzamide (236), prepared in ee steps from commercially available 2,4,S-trimethoxybenzoic acid (237) via o-lithiation of the corresponding amide and subsequent iodination. Benzylation of 235 to 238 was followed by phosphoryl diloride cyclization and hydrolysis of the intermechate with aqueous hydrochloric acid to give 5 benzyloxy-l,3,4-trimethoxyacridone (239) as the major product. Methylation to 5-be izylo3 -l,3,4-trimethoxy-10-methylacridone (240), followed by simultaneous hydrolysis of the benzyloxy group, and of the methoxy group at C-1, gave citrusinine-I I (64). 

Synthesis of 1,2,3-trimethoxy-10-methylacridone (73) and evoxanthine (13) by the same approach necessitated the preparation of 4,5,6-trimethoxy-iV-methyl-isatoic anhydride (262) and 6-methoxy-4,5-methylenedioxy-7V-methylisatoic anhydride (263). Nitration of 2,3,4-trimethoxybenzoic acid (264) afforded 6-nitro-... 

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